tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of Empagliflozin in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Jimmy Zheng, Justin T. Parizo, John A. Spertus, Paul A. Heidenreich, Alexander T. Sandhu
Journal: JAMA Internal Medicine (2022)

In the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved), empagliflozin significantly reduced hospitalizations for heart failure while improving patient-reported health status compared with placebo. The long-term cost-effectiveness of empagliflozin among patients who have heart failure with preserved ejection fraction (HFpEF) remains unclear.To estimate the cost-effectiveness of empagliflozin in patients with HFpEF.This cost-effectiveness analysis performed from October 2021 to April 2022 included a Markov model using estimates of treatment efficacy, event probabilities, and utilities from EMPEROR-Preserved and published literature. Costs were derived from national surveys and pricing data sets. Quality of life was imputed from a heart failure-specific quality-of-life measure. Two analyses were performed, with and without a treatment effect on cardiovascular mortality. Subgroup analyses were based on diabetes status, ejection fraction, and health status impairment due to heart failure. The model reproduced the event rates and risk reduction with empagliflozin observed in EMPEROR-Preserved over 26 months of follow-up; future projections extended across the lifetime of patients.Empagliflozin or standard of care.Hospitalizations for heart failure, life-years, quality-adjusted life-years (QALYs), lifetime costs, and lifetime incremental cost-effectiveness ratio.A total of 5988 patients were included in the analysis, with a mean age of 72 years, New York Heart Association class II to IV heart failure, and left ventricular ejection fraction greater than 40%. At the Federal Supply Schedule price of $327 per month, empagliflozin yielded 0.06 additional QALYs and $26 257 incremental costs compared with standard of care, producing a cost per QALY gained of $437 442. Incremental costs consisted of total drug costs of $29 586 and savings of $3329 from reduced hospitalizations for heart failure. Cost-effectiveness was similar across subgroups. The results were most sensitive to the monthly cost, quality-of-life benefit, and mortality effect of empagliflozin. A price reduction to $153 per month, incremental utility of 0.02, or 8% reduction in cardiovascular mortality would bring empagliflozin to $180 000 per QALY gained, the threshold for intermediate value. Using Medicare Part D monthly pricing of $375 after rebates and $511 before rebates, empagliflozin would remain low value at $509 636 and $710 825 per QALY gained, respectively. Cost-effectiveness estimates were robust to variation in the frequency and disutility of heart failure hospitalizations.In this economic evaluation, based on current cost-effectiveness benchmarks, empagliflozin provides low economic value compared with standard of care for HFpEF, largely due to its lack of efficacy on mortality and small benefit on quality of life.
Is There a Real Association of Racial Disparities With In-Hospital Outcomes in Severe Bronchopulmonary Dysplasia?—Reply
Authors: Matthew J. Kielt, Tamorah R. Lewis
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Loss of bisecting GlcNAcylation on MCAM of bone marrow stoma determined pro-tumoral niche in MDS/AML
Authors: Jingjing Feng, Yi Wang, Bingxin Li, Xinwen Yu, Lei Lei, Jinpeng Wu, Xin Zhang, Qiushi Chen, Yue Zhou, Junjie Gou, Hongjiao Li, Zengqi Tan, Zhijun Dai, Xiang Li, Feng Guan
Journal: Leukemia (2022)
Nitric Oxide Scavenging and Hydrogen Sulfide Production Synergistically Treat Rheumatoid Arthritis
Authors: Wenbo Geng, Xuezhe Liu, Bailong Tao, Ye He, Ke Li, Pengfei Gao, Qian Feng, Peng Zhao, Zhong Luo, Kaiyong Cai
Journal: Advanced Healthcare Materials (2022)

Abstract To restore the disordered endogenous gas levels is an efficient alternative for the treatment of rheumatoid arthritis (RA). Both insufficient hydrogen sulfide (H 2 S) and excessive nitric oxide (NO) contribute to synovial inflammation. Herein, a new block polymer PEG 10 ‐ b ‐PNAPA 30 ‐ b ‐PEG 10 composed of an NO‐responsive monomer and a cysteine‐triggered H 2 S donor, which can simultaneously scavenge NO and release therapeutic H 2 S for RA treatment, is reported. In vitro experiments demonstrate that the polymer exhibits a synergistic effect on suppressing reactive oxygen species levels and pro‐inflammatory cytokine production via NF‐ κ B signaling pathway. It leads to the polarization of macrophages from M1 to M2 phenotype. Moreover, the released H 2 S further restrains NO production by suppressing the expression of iNOS. In vivo experiments with an RA rat model show that the system markedly mitigates the synovial inflammation, osteoporosis, and clinical symptoms of RA rats, which is attributed to the combination therapy of H 2 S release and NO depletion. This work provides new insight into the synergistic treatment of RA and endogenous gas‐related diseases.
Daily Low-Dose Aspirin and Risk of Serious Falls and Fractures in Healthy Older People
Authors: Anna L. Barker, Renata Morello, Le Thi Phuong Thao, Ego Seeman, Stephanie A. Ward, Kerrie M. Sanders, Robert G. Cumming, Julie A. Pasco, Peter R. Ebeling, Robyn L. Woods, Rory Wolfe, Sundeep Khosla, Sultana Monira Hussain, Kathlyn Ronaldson, Anne B. Newman, Jeff D. Williamson, John J. McNeil
Journal: JAMA Internal Medicine (2022)

Importance Falls and fractures are frequent and deleterious to the health of older people. Aspirin has been reported to reduce bone fragility and slow bone loss. Objective To determine if daily low-dose aspirin (100 mg) reduces the risk of fractures or serious falls (fall-related hospital presentations) in healthy older men and women. Design, Setting, and Participants This substudy of a double-blind, randomized, placebo-controlled trial studied older adult men and women in 16 major sites across southeastern Australia. The ASPREE-FRACTURE substudy was conducted as part of the Australian component of the ASPREE trial. Between 2010 and 2014 healthy (free of cardiovascular disease, dementia or physical disability), community-dwelling volunteers aged 70 years or older were recruited to participate in the ASPREE trial. Potentially eligible participants were identified by medical practitioners and trial personnel and were then sent a letter of invitation to participate. Interested participants were screened for suitability. Eligible participants with medical practitioner authorization and adherent to a 4-week run-in medication trial were randomized. Data were analyzed from October 17, 2019, to August 31, 2022. Interventions Participants in the intervention group received a daily dose of oral 100 mg enteric-coated (low-dose) aspirin. The control group received a daily identical enteric-coated placebo tablet. Main Outcomes and Measures The primary outcome of ASPREE-FRACTURE was the occurrence of any fracture. The secondary outcome was serious fall resulting in hospital presentation. Results In total, 16 703 people with a median (IQR) age of 74 (72-78) years were recruited, and 9179 (55.0%) were women. There were 8322 intervention participants and 8381 control participants included in the primary and secondary outcome analysis of 2865 fractures and 1688 serious falls over the median follow-up of 4.6 years. While there was no difference in the risk of first fracture between the intervention and control participants (hazard ratio, 0.97; 95% CI, 0.87-1.06; P = .50), aspirin was associated with a higher risk of serious falls (total falls 884 vs 804; incidence rate ratio, 1.17; 95% CI, 1.03-1.33; P = .01). Results remained unchanged in analyses that adjusted for covariates known to influence fracture and fall risk. Conclusions and Relevance In this substudy of a randomized clinical trial, the failure of low-dose aspirin to reduce the risk of fractures while increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population. Trial Registration This substudy is registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615000347561 ).
Rate of Recurrence After Discontinuing Anticoagulation Therapy in Patients With COVID-19–Associated Venous Thromboembolism
Authors: Luis Jara-Palomares, Behnood Bikdeli, David Jiménez, Alfonso Muriel, Mar Martin del Pozo, Pablo Demelo-Rodríguez, Manuel Monreal
Journal: JAMA Internal Medicine (2022)

This cohort study assesses the rate of recurrence of venous thromboembolism (VTE) in patients with COVID-19–associated VTE who discontinued anticoagulation therapy.
Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk
Authors: Aruna Das Pradhan, Robert J. Glynn, Jean-Charles Fruchart, Jean G. MacFadyen, Elaine S. Zaharris, Brendan M. Everett, Stuart E. Campbell, Ryu Oshima, Pierre Amarenco, Dirk J. Blom, Eliot A. Brinton, Robert H. Eckel, Marshall B. Elam, João S. Felicio, Henry N. Ginsberg, Assen Goudev, Shun Ishibashi, Jacob Joseph, Tatsuhiko Kodama, Wolfgang Koenig, Lawrence A. Leiter, Alberto J. Lorenzatti, Boris Mankovsky, Nikolaus Marx, Børge G. Nordestgaard, Dénes Páll, Kausik K. Ray, Raul D. Santos, Handrean Soran, Andrey Susekov, Michal Tendera, Koutaro Yokote, Nina P. Paynter, Julie E. Buring, Peter Libby, Paul M Ridker
Journal: New England Journal of Medicine (2022)

High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator–activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.
4D Printing of Overall Radiopaque Customized Bionic Occlusion Devices
Authors: Cheng Lin, Zhipeng Huang, Qinglong Wang, Zhichen Zou, Wenbo Wang, Liwu Liu, Yanju Liu, Jinsong Leng
Journal: Advanced Healthcare Materials (2022)

Abstract Percutaneous closure of ventricular septal defect (VSD) can effectively occlude abnormal blood flow between ventricles. However, commonly used Nitinol occlusion devices have non‐negligible limitations, such as nondegradability leading to life‐threatening embolization; limited device size predisposing to displacement and wear; only a few radiopaque markers resulting in inaccurate positioning. Nevertheless, the exploration of customized, biodegradable, and overall radiopaque occluders is still vacant. Here, overall radiopaque, biodegradable, and dynamic reconfigurable 4D printed VSD occluders are developed. Based on wavy bionic structures, various VSD occluders are designed and manufactured to adapt to the position diversity of VSD. The customized configuration, biocompatibility, and biodegradability of the developed 4D printed bionic occluders can eliminate the series of complications caused by traditional occluders. The overall radiopacity of 4D printed VSD occluders is validated ex vivo and in vivo, whereby accurate positioning can be assured. Notably, the preparation strategies for 4D printed occluders are scalable, eliminating the barriers to mass production, and marking a meaningful step in bridging the gap between modeling and clinical application of 4D printed occlusion devices. This work opens attractive perspectives for the rapid manufacturing of customized intelligent medical devices for which overall radiopacity, dynamic reconfigurability, biocompatibility, and biodegradability are sought.
Continuous Positive Airway Pressure Effect on Albuminuria Progression in Patients with Obstructive Sleep Apnea and Diabetic Kidney Disease: A Randomized Clinical Trial
Authors: Ester Zamarrón, Ana Jaureguizar, Aldara García-Sánchez, Trinidad Díaz-Cambriles, Alberto Alonso-Fernández, Vanesa Lores, Olga Mediano, Fernanda Troncoso-Acevedo, Sheila Cabello-Pelegrín, Enrique Morales-Ruíz, María T. Ramírez-Prieto, María Isabel Valiente-Díaz, Teresa Gómez-García, Raquel Casitas, Elisabet Martínez-Cerón, Raúl Galera, Carolina Cubillos-Zapata, Francisco García-Río
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic kidney disease (DKD). However, the effect of apnea-hypopnea suppression on DKD progression is unclear. Objectives: To assess the effect of continuous positive airway pressure (CPAP) on the urinary albumin-to-creatinine ratio (UACR) in patients with DKD and OSA. Methods: In a 52-week, multicentric, open-label, parallel, and randomized clinical trial, 185 patients with OSA and DKD were randomized to CPAP and usual care (n = 93) or usual care alone (n = 92). Measurements and Main Results: UACR, estimated glomerular filtration rate, serum concentrations of creatinine and glycated hemoglobin, insulin resistance, lipid concentrations, sleepiness, and quality of life. A 52-week change in UACR from baseline did not differ significantly between the CPAP group and the usual-care group. However, in per-protocol analyses that included 125 participants who met prespecified criteria for adherence, CPAP treatment was associated with a great reduction in UACR (mean difference, -10.56% [95% confidence interval, -19.06 to -2.06]; P = 0.015). CPAP effect on UACR was higher in nonsleepy patients with more severe OSA, worse renal function, and a more recent diagnosis of DKD. CPAP treatment also improved glycemic control and insulin resistance, as well as sleepiness and health-related quality of life. Conclusions: In patients with OSA and DKD, the prescription of CPAP did not result in a statistically significant reduction in albuminuria. However, good adherence to CPAP treatment in addition to usual care may result in long-term albuminuria reduction compared with usual care alone. Clinical trial registered with www.clinicaltrials.gov (NCT02816762).
Assessment of Changes in Child and Adolescent Screen Time During the COVID-19 Pandemic
Authors: Sheri Madigan, Rachel Eirich, Paolo Pador, Brae Anne McArthur, Ross D. Neville
Journal: JAMA Pediatrics (2022)

To limit the spread of COVID-19, numerous restrictions were imposed on youths, including school closures, isolation requirements, social distancing, and cancelation of extracurricular activities, which independently or collectively may have shifted screen time patterns.To estimate changes in the duration, content, and context of screen time of children and adolescents by comparing estimates taken before the pandemic with those taken during the pandemic and to determine when and for whom screen time has increased the most.Electronic databases were searched between January 1, 2020, and March 5, 2022, including MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials. A total of 2474 nonduplicate records were retrieved.Study inclusion criteria were reported changes in the duration (minutes per day) of screen time before and during the pandemic; children, adolescents, and young adults (≤18 years); longitudinal or retrospective estimates; peer reviewed; and published in English.A total of 136 articles underwent full-text review. Data were analyzed from April 6, 2022, to May 5, 2022, with a random-effects meta-analysis.Change in daily screen time comparing estimates taken before vs during the COVID-19 pandemic.The meta-analysis included 46 studies (146 effect sizes; 29 017 children; 57% male; and mean [SD] age, 9 [4.1] years) revealed that, from a baseline prepandemic value of 162 min/d (2.7 h/d), during the pandemic there was an increase in screen time of 84 min/d (1.4 h/d), representing a 52% increase. Increases were particularly marked for individuals aged 12 to 18 years (k [number of sample estimates] = 26; 110 min/d) and for device type (handheld devices [k = 20; 44 min/d] and personal computers [k = 13; 46 min/d]). Moderator analyses showed that increases were possibly larger in retrospective (k = 36; 116 min/d) vs longitudinal (k = 51; 65 min/d) studies. Mean increases were observed in samples examining both recreational screen time alone (k = 54; 84 min/d) and total daily screen time combining recreational and educational use (k = 33; 68 min/d).The COVID-19 pandemic has led to considerable disruptions in the lives and routines of children, adolescents, and families, which is likely associated with increased levels of screen time. Findings suggest that when interacting with children and caregivers, practitioners should place a critical focus on promoting healthy device habits, which can include moderating daily use; choosing age-appropriate programs; promoting device-free time, sleep, and physical activity; and encouraging children to use screens as a creative outlet or a means to meaningfully connect with others.
Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension
Authors: Mason W. Freeman, Yuan-Di Halvorsen, William Marshall, Mackenzie Pater, Jon Isaacsohn, Catherine Pearce, Brian Murphy, Nicholas Alp, Ajay Srivastava, Deepak L. Bhatt, Morris J. Brown
Journal: New England Journal of Medicine (2022)

Aldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels.In this multicenter, placebo-controlled trial, we randomly assigned patients who had treatment-resistant hypertension, with blood pressure of 130/80 mm Hg or higher, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The primary end point was the change in systolic blood pressure from baseline to week 12 in each baxdrostat group as compared with the placebo group.A total of 248 patients completed the trial. Dose-dependent changes in systolic blood pressure of -20.3 mm Hg, -17.5 mm Hg, -12.1 mm Hg, and -9.4 mm Hg were observed in the 2-mg, 1-mg, 0.5-mg, and placebo groups, respectively. The difference in the change in systolic blood pressure between the 2-mg group and the placebo group was -11.0 mm Hg (95% confidence interval [CI], -16.4 to -5.5; P<0.001), and the difference in this change between the 1-mg group and the placebo group was -8.1 mm Hg (95% CI, -13.5 to -2.8; P = 0.003). No deaths occurred during the trial, no serious adverse events were attributed by the investigators to baxdrostat, and there were no instances of adrenocortical insufficiency. Baxdrostat-related increases in the potassium level to 6.0 mmol per liter or greater occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug.Patients with treatment-resistant hypertension who received baxdrostat had dose-related reductions in blood pressure. (Funded by CinCor Pharma; BrigHTN ClinicalTrials.gov number, NCT04519658.).
Sintilimab versus docetaxel as second‐line treatment in advanced or metastatic squamous non‐small‐cell lung cancer: an open‐label, randomized controlled phase 3 trial (ORIENT‐3)
Authors: Yuankai Shi, Lin Wu, Xinmin Yu, Puyuan Xing, Yan Wang, Jianying Zhou, Airong Wang, Jianhua Shi, Yi Hu, Ziping Wang, Guangyu An, Yong Fang, Sanyuan Sun, Caicun Zhou, Changli Wang, Feng Ye, Xingya Li, Junye Wang, Mengzhao Wang, Yunpeng Liu, Yanqiu Zhao, Ying Yuan, Jifeng Feng, Zhendong Chen, Jindong Shi, Tao Sun, Gang Wu, Yongqian Shu, Qisen Guo, Yi Zhang, Yong Song, Shucai Zhang, Yuan Chen, Wei Li, Hongrui Niu, Wenwei Hu, Lijun Wang, Jianan Huang, Yang Zhang, Ying Cheng, Zhengdong Wu, Bo Peng, Jiya Sun, Christoph Mancao, Yanqi Wang, Luyao Sun
Journal: Cancer Communications (2022)

Abstract Background Treatment options for Chinese patients with locally advanced or metastatic squamous‐cell non‐small‐cell lung cancer (sqNSCLC) after failure of first‐line chemotherapy are limited. This study (ORIENT‐3) aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second‐line treatment in patients with locally advanced or metastatic sqNSCLC. Methods ORIENT‐3 was an open‐label, multicenter, randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first‐line platinum‐based chemotherapy. Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m 2 of docetaxel intravenously every 3 weeks, stratified by the Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Results Between August 25, 2017, and November 7, 2018, 290 patients were randomized. For FAS, 10 patients from the docetaxel arm were excluded. The median OS was 11.79 ( n = 145; 95% confidence interval [CI], 10.28‐15.57) months with sintilimab versus 8.25 ( n = 135; 95% CI, 6.47‐9.82) months with docetaxel (hazard ratio [HR]: 0.74; 95% CI, 0.56‐0.96; P = 0.025). Sintilimab treatment significantly prolonged PFS (median 4.30 vs. 2.79 months; HR: 0.52; 95% CI, 0.39‐0.68; P &lt; 0.001) and showed higher ORR (25.50% vs. 2.20%, P &lt; 0.001) and DCR (65.50% vs. 37.80%, P &lt; 0.001) than the docetaxel arm. The median DoR was 12.45 (95% CI, 4.86‐25.33) months in the sintilimab arm and 4.14 (95% CI, 1.41‐7.23) months in the docetaxel arm ( P = 0.045). Treatment‐related adverse events of grade ≥ 3 were reported in 26 (18.1%) patients in the sintilimab arm and 47 (36.2%) patients in the docetaxel arm. Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors, including OVOL2 (HR: 0.35; P &lt; 0.001) and CTCF (HR: 3.50; P &lt; 0.001)，for sintilimab treatment. Conclusions Compared with docetaxel, sintilimab significantly improved the OS, PFS, and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.